Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J

Membrane-bound phosphoinositides are signalling molecules that have a key role in vesicle trafficking in eukaryotic cells. Proteins that bind specific phosphoinositides mediate interactions between membrane-bounded compartments whose identity is partially encoded by cytoplasmic phospholipid tags. Little is known about the localization and regulation of mammalian phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), a phospholipid present in small quantities that regulates membrane trafficking in the endosome-lysosome axis in yeast. Here we describe a multi-organ disorder with neuronal degeneration in the central nervous system, peripheral neuronopathy and diluted pigmentation in the 'pale tremor' mouse. Positional cloning identified insertion of ETn2beta (early transposon 2beta) into intron 18 of Fig4 (A530089I17Rik), the homologue of a yeast SAC (suppressor of actin) domain PtdIns(3,5)P2 5-phosphatase located in the vacuolar membrane. The abnormal concentration of PtdIns(3,5)P2 in cultured fibroblasts from pale tremor mice demonstrates the conserved biochemical function of mammalian Fig4. The cytoplasm of fibroblasts from pale tremor mice is filled with large vacuoles that are immunoreactive for LAMP-2 (lysosomal-associated membrane protein 2), consistent with dysfunction of the late endosome-lysosome axis. Neonatal neurodegeneration in sensory and autonomic ganglia is followed by loss of neurons from layers four and five of the cortex, deep cerebellar nuclei and other localized brain regions. The sciatic nerve exhibits reduced numbers of large-diameter myelinated axons, slowed nerve conduction velocity and reduced amplitude of compound muscle action potentials. We identified pathogenic mutations of human FIG4 (KIAA0274) on chromosome 6q21 in four unrelated patients with hereditary motor and sensory neuropathy. This novel form of autosomal recessive Charcot-Marie-Tooth disorder is designated CMT4J.     

Water,a powerful attractant for the gravid females of Plodia interpunctella and Cadra cautella

Summary In the sex pheromone controlling experiments, not only large number of the males of the almond moth and Indian meal moth, but also great number of ovipositional females were caught. The increased catch of the fertilized females was due to the presence of detergent in the water.     

HIGHER-ORDER PETRI NET MODELS BASED ON ARTIFICIAL NEURAL NETWORKS

提出了一种新型Ｐｅｔｒｉ网———高阶Ｐｅｔｒｉ网，这种网可以应用于一阶谓词逻辑中的多项式子句集问题；还研究了目标转移结点Ｔ－不变量之间的关系，最后给出了几个例子。     

Role of low ecdysteroid levels in the early last larval instar ofBombyx mori

The relationship between juvenile hormone and ecdysteroid titers during the early stage of the last larval instar of the silkworm,Bombyx mori, was examined in this study. When larvae were fed 20-hydroxyecdysone-supplemented mulberry leaves throughout the last larval instar, 100% underwent supernumerary larval molting instead of metamorphosis. The application of juvenile hormone mimic during the early last instar did not induce supernumerary larval molting, but did delay metamorphosis. Temporal and quantitative ecdysteroid titer measurements revealed that in normal larvae the titers maintained very low levels (3–12 ng/ml) during the early stage of the last instar; however, in 20-hydroxyecdysone-treated larvae, levels ranging from 24 to 45 ng/ml were detected, and a major peak (246 ng/ml) was observed on day 6. These results show that very low ecdysteroid titer levels during the early stage of the last larval instar may play an important role in initiating decreases in juvenile hormone titers as well as in directing metamorphosis.     

Possible mechanism of rubidium-induced hyperactivity in the rat.

This study suggests that replacement of intracellular potassium by rubidium ions might lower the resting membrane potential. Thus rubidium-treated rats were more responsive to depolarizing influences and generated more cyclic AMP in the brainstem and consequently the behavioral changes.     

Three-dimensional control of light in a two-dimensional photonic crystal slab

Optoelectronic devices are increasingly important in communication and information technology. To achieve the necessary manipulation of light (which carries information in optoelectronic devices), considerable efforts are directed at the development of photonic crystals--periodic dielectric materials that have so-called photonic bandgaps, which prohibit the propagation of photons having energies within the bandgap region. Straightforward application of the bandgap concept is generally thought to require three-dimensional (3D) photonic crystals; their two-dimensional (2D) counterparts confine light in the crystal plane, but not in the perpendicular z direction, which inevitably leads to diffraction losses. Nonetheless, 2D photonic crystals still attract interest because they are potentially more amenable to fabrication by existing techniques and diffraction losses need not seriously impair utility. Here we report the fabrication of a waveguide-coupled photonic crystal slab (essentially a free-standing 2D photonic crystal) with a strong 2D bandgap at wavelengths of about 1.5 microm, yet which is capable of fully controlling light in all three dimensions. These features confirm theoretical calculations on the possibility of achieving 3D light control using 2D bandgaps, with index guiding providing control in the third dimension, and raise the prospect of being able to realize unusual photonic-crystal devices, such as thresholdless lasers.     

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not.     

A protective role for protease-activated receptors in the airways

The protection of cells in the upper intestine against digestion by pancreatic trypsin depends on the prostanoid prostaglandin E2 (PGE2) and is mediated by protease-activated receptors in the epithelium. As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2, and is a major source of PGE2, we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways. Here we show that activation of PAR2, which co-localizes immunohistochemically with trypsin(ogen) in airway epithelium, causes the relaxation of airway preparations from mouse, rat, guinea-pig and humans by the release of a cyclooxygenase product from the epithelium. This physiological protective response in isolated airways also occurred in anaesthetized rats, where activation of PAR2 caused a marked and prolonged inhibition of bronchoconstriction. After desensitization of PAR2, the response to trypsin recovered rapidly by mechanisms dependent on de novo synthesis and trafficking of proteins. Our results indicate that trypsin released from the epithelium can initiate powerful bronchoprotection in the airways by activation of epithelial PAR2.     

A Robust Test for Threshold‐Type Nonlinearity in Multivariate Time Series Analysis

There is growing interest in exploring potential forecast gains from the nonlinear structure of multivariate threshold autoregressive (MTAR) models. A least squares‐based statistical test has been proposed in the literature. However, previous studies on univariate time series analysis show that classical nonlinearity tests are often not robust to additive outliers. The outlier problem is expected to pose similar difficulties for multivariate nonlinearity tests. In this paper, we propose a new and robust MTAR‐type nonlinearity test, and derive the asymptotic null distribution of the test statistic. A Monte Carlo experiment is carried out to compare the power of the proposed test with that of the least squares‐based test under the influence of additive time series outliers. The results indicate that the proposed method is preferable to the classical test when observations are contaminated by outliers. Finally, we provide illustrative examples by applying the statistical tests to two real datasets. Copyright © 2015 John Wiley & Sons, Ltd.